The objective of the proposed research is to devise a new, versatile procedure for the total synthesis of iboga and aspidosperma alkaloids. Our goal is to develop a method that would be general enough to permit the synthesis of a variety of iboga and aspidosperma alkaloids, that would generate 2,3-disubstituted indoles from readily available 3-substituted indoles, and that would directly incorporate the requisite C(16) carbomethoxy group into the molecule. The iboga alkaloid catharanthine and the aspidosperma alkaloid vindoline are the specific synthetic targets of the endeavor. Research directed toward the synthesis of the anti-leukemic bisindole alkaloids via the coupling of iboga and aspidosperma alkaloids is underway successfully in several laboratories. The crux of our synthetic approach involves the Claisen ortho ester rearrangement of 3-indoleglycolic acid derivatives with appropriate ortho esters to give the 2,3-disubstituted indoles that contain both the crucial C(16) carbomethoxy group found in many iboga and aspidosperma alkaloids, and the functionality necessary for elaboration to those alkaloids. This transformation should provide a versatile procedure for the total synthesis of iboga and aspidosperma alkaloids since both the necessary 3-indoleglycolic acid derivatives and ortho esters are readily available, since the Claisen ortho ester rearrangement proceeds under mild reaction conditions which are compatible with a wide variety of functionality, and since methods for the elaboration of the 2,3-disubstituted indoles should be quite straight forward.